title: In vitro and in vivo evaluation of novel immediate release carbamazepine tablets: complexation with hydroxypropyl-β-cyclodextrin in the presence of HPMC.
abstract: Carbamazepine (CBZ)-hydroxypropyl-β-cyclodextrin (HP-β-CD) complex in the presence of HPMC was prepared and characterized by differential scanning calorimetry (DSC) and X-ray diffractometer intended for improving the dissolution rate of CBZ. The phase-solubility method was used to investigate the effect of HP-β-CD and HPMC on the solubility of CBZ. Tablets of the resulting complex were prepared using direct compression method and the bioavailability was evaluated in beagle dogs using a UPLC/MS/MS method. The results showed solubility of CBZ was increased up to 95 times by complexation with HP-β-CD in the presence of 0.1% HPMC. The results of DSC and X-ray diffraction proved a formation of complex between CBZ and HP-β-CD. Dissolution rate of CBZ was notably improved from complex tablets with more than 97.39% released within 10 min; whereas for the commercial tablets, around 60% was released within 30 min. Using commercial tablets as the reference formulation, the bioavailability of complex tablets was considerably increased by 1.5-fold (P<0.05) and T(max) was reduced to 0.88 h compared with 1.25 h for commercial tablets. Furthermore, a lower inter-subject variability (49.9%) was observed compared with that of the commercial tablets (39.7%). It is evident from the results herein that complexation with HP-β-CD in the presence of HPMC is a feasible way to prepare a rapidly acting and better absorbed CBZ oral product.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Mailbox 59#, 103 Wenhua Road, Shenyang 110016, Liaoning Province, PR China. kouwen1224@126.com
authors.forename: Wen
authors.initials: W
authors.lastname: Kou
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
authors.forename: Shuying
authors.initials: S
authors.lastname: Xu
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Tianhong
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods; D004285:Dogs; D005079:Excipients / Q000737:chemistry*; D005260:Female; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D012995:Solubility; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods; D013997:Time Factors; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000927:Anticonvulsants; D005079:Excipients; D013607:Tablets; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002220:Carbamazepine; D065347:Hypromellose Derivatives; D008747:Methylcellulose